The Baylor College of Medicine Human Genome Sequencing Center (BCM-HGSC) will apply a scalable, high-throughput DNA sequencing process to the generation of more than 420 Mb of genomic sequence coverage of the mouse. 27 Mb of the sequence will be finished, with an estimated accuracy of less than 1 error per 10,000 bases. The sequencing will be guided by a low cost partial mapping hybridization approach for selection of seed clones, and a simplified fingerprinting method that will yield a whole genome map. These mapping efforts will provide a public resource that will assist all groups in the rational selection of a minimal set of high integrity clones for sequencing, and will greatly speed the eventual closing and finishing of the genome. The sequence production will rely heavily on an automated platform that integrates commercially available devices, machines developed locally, and established BCM-HGSC sequencing protocols. New Perkin-Elmer 3700 capillary DNA sequencers will be used to boost throughput, and the entire activity will be housed in new space, custom built for the BCM-HGSC. The sequence drafting will be at 5X coverage which provides the best balance between low cost, high throughput, maximum data utility and ease of sequence finishing. All sequence data will be placed immediately in the public domain. To understand the mouse sequence better, human-mouse sequence comparisons will be carried out using available tools, and a new cross-species integrative approach based on hierarchic recognition of sequence. The new sequence comparison methods will be appropriate for both finished and draft sequence studies.